Uses of Quetiapine

Welcome

Clinical Uses of Quetiapine

Presented by:

Dr. S.M. Yasir Arafat

Phase A Resident

Psychiatry, BSMMU

August 06, 2014.

Quetiapine

dibenzothiazepine antipsychotic

Serotonin-Dopamine Anatagonist

tablet dosage form

available in 25 & 100 mg

developed by Zeneca

approved by FDA on 1997

Available preparations in BD

SI. No. Brand Company Strength Price

1. Qpine Sanofi 25 & 100 mg 3 & 10 Tk

2. Quiet Incepta 25 & 100 mg 3 & 10 Tk

3. Tiapine General 100 mg 10 Tk

4. Quitipin Sun 25 & 100 mg 3 & 10 Tk

5. Seroquet Unimed 25 & 100 mg 3 & 10 Tk

What lacks in BD

XR preparations

• D2, 5-HT2, 5-HT6, D1, H1, α1, α2

• Sedative

• Anxiolytic

• Antimanic

• Mood-stabilizing

• Antidressant

Mode of action

Clinical Uses- FDA Approved

Acute Schizophrenia in adults & ages 13-17 years

Schizophrenia maintenance

Acute Mania in adults & ages 10-17 years

Bipolar maintenance

Bipolar depression

Depression (Adjunct)

Clinical Uses- Off LabelMixed maniaBehavioral disturbance in dementiasBehavioral disturbance in Parkinson’s disease

and Lewy body dementiaPsychosis associated with levodopa treatment in

Parkinson’s diseaseBehavioral disturbances in children and

adolescentsDisorders associated with impulse controlSevere treatment resistant anxiety

How Long Until It Works• Psychotic & Manic symptoms may improve in

1week• Cognition, Behavior change & Affective

stabilization- several weeks• Classically recommended to wait 4-6 weeks• May take 16-20 weeks• It is often under dosed & switched prior to

adequate trials• Efficacy may be underestimated due to

underdosed

Dosage guideline…

Initial dose of 25mg bid, with increase in increments of 25-50 mg on second and third day as tolerated, to a target dose of 300-400 mg by fourth day

depending on clinical response and tolerability dose may be adjusted within range of 300-800 mg/day

Initial gradual upward titration is helpful to reduce side effects

In reality, more aggressive dosing is both tolerated & effective

Schizophrenia & Quetiapine

Dose: 25 mg twice daily on day 1 50 mg twice daily on day 2 100 mg twice daily on day 3 150 mg twice daily on day 4

Then adjusted according to response, usual range 300–450 mg daily in 2 divided doses

Max. 800 mg daily

Schizophrenia & QuetiapineRecent Update 1• Johnsen et al. BMC Psychiatry 2010, 10:26• Effectiveness of second-generation antipsychotics: a

naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone

• Patients acutely admitted to hospital for symptoms of psychosis, the quetiapine group was associated with the most beneficial outcome in terms of reduction of the PANSS total score; the PANSS positive subscale score; the PANSS general psychopathology subscale score; the CGI-S score; and in increasing the GAF-F score.

Schizophrenia & Quetiapine

Recent Update 2 (Memory)• Riedel et al, 2010• Hum. Psychopharmacol Clin Exp 2010; 25: 116–

125.Neurocognition and its influencing factors in the treatment of schizophrenia—effects of aripiprazole, olanzapine, quetiapine and risperidone

• Quetiapine was found to improve working memory significantly better than risperidone, olanzapine and aripiprazole

Schizophrenia & Quetiapine

Facts in Schizoprenia• Reduces positive symptoms but doesn’t

eliminate• Most Schizoprenics don’t have total remission,

reduction of symptoms by third• Long time treatment needed to prevent

subsequent episodes

Mania & Quetiapine Quetiapine has robust efficacy in all aspects of Bipolar

disorder Dose:

50 mg twice daily on day 1. 100 mg twice daily on day 2. 150 mg twice daily on day 3. 200 mg twice daily on day 4. Then adjusted according to response in steps of up to

200 mg daily to max. 800 mg daily. Usual range 400–800 mg daily in 2 divided doses.

Bipolar depression & Quetiapine

• 1st choice treatment option is Quetiapine• The usual dose is 300 mg/day

25 mg twice daily on day 1 50 mg twice daily on day 2 100 mg twice daily on day 3 150 mg twice daily on day 4

• Then can be titrated to 400 mg on Day 5 and up to 600 mg by Day 8.

Recent Update 1 Alessandra et al, 2011 Journal of Affective Disorders (Review)

Volume 129, Issues 1–3, March 2011, Pages 14–26 New treatment guidelines for acute bipolar depression: A

systematic review The latest updates on treatment guidelines for bipolar

depression give priority to novel treatment approaches, such as quetiapine, over more traditional ones, such as lithium or antidepressants. Lamotrigine is a controversial option.

Bipolar depression & Quetiapine

Recent Update 2• Sanford & Gillian, 2012• CNS Drugs- Quetiapine• May 2012, Volume 26, Issue 5, pp 435-460 • Quetiapine and quetiapine XR are valuable

additions to the first-line treatments for bipolar depression. Further head-to-head trials of quetiapine versus other drug regimens that are effective in bipolar depression would be of considerable interest.

Bipolar depression & Quetiapine

Bipolar prophylaxis

1st line: Lithium, Olanzapine, Quetiapine, Aripiprazole

Unipolar Resistant Depression

• As an adjunct• 150mg or 300 mg daily to SSRI/ SNRI

Others

• In doses of 25 to 300 mg at night has been used for insomnia.

Over dose :

• Signs and symptoms of overdose : Lethargy, tachycardia QT prolongation Respiratory distress Depression, hypotension Sedation Slurring of speech

• Overdose is not common• No specific antidote• Only symptomatic treatment needed

Alternatives to clozapine:Treatment Comments

Quetiapine Very limited evidence and clinical experience not encouraging. Highdoses

(>1200mg/day) have been used

Quetiapine + haloperidol

Two case reports

How to Stop

• Slow down titration (over 6-8 wks) in cross titration

• Rapid discontinuation- rebound psychosis

Conclusion Only antipsychotic approved for all phases and types of

bipolar disorder Drug of choice for managing Bipolar depression Indicated as monotherapy for depressive episodes

associated with bipolar disorder Quetiapine is the most costly antipsychotic in higher

dose

Reference

1. British National Formulary

2. Kaplan & Sadock's Synopsis of Psychiatry:

Behavioral Sciences/Clinical Psychiatry, 10th Edition

3. Kaplan & Sadock's Pocket Handbook of Psychiatric

Drug Treatment, 5th Edition

4. The Maudsley, Prescribing Guidelines, 11th Edition

5. Stahl’s Essential Psychopharmacology, 4th Edition

6. Different journals

7. Product Data Sheet